CX3CR1 regulates hepatocellular carcinoma(HCC) metastasis via PI3K/AKT pathway

Abstract

Background Fractalkine receptor CX3CR1 is differentially expressed in hepatocellular carcinoma and its function is unknown. As a special case of chemokine family, CX3CR1 only binds to its unique ligand CX3CL1, and CX3CL1 also only binds to its only receptor CX3CR1, the unique matching between ligands and receptors is not found in other chemokines, and this specificity is essential for diagnosis, prognosis and clinical target therapy. Methods CX3CR1 expression was analyzed by immunohistochemistry, migration and invasion abilities of SMMC-7721 cells were detected by wound-healing and transwell after overexpressing CX3CR1. In addition to overexpression experiments, interfering RNA siCX3CR1 was used for reverse validation in HepG2 cells. To further clarify the mechanism of CX3CR1 regulating HCC metastasis, the classical PI3K/AKT pathway were detected by Western blot. Results The CX3CR1 levels were positive correlated with pathological TNM stage, meanwhile a negative correlation between high expression of CX3CR1 and survival rate was found among patients at stageII-III. In our study, overexpression of CX3CR1 promoted migration and invasion ability of SMMC-7721 cells, whereas knockout of CX3CR1 inhibited these abilities of HepG2 cells. Mechanistically, CX3CR1 regulates the metastasis of HCC cells via PI3K/AKT pathway, and the PI3K inhibitor LY294002 could stop the promoting effect of CX3CR1 on SMMC-7721 cells. Conclusion CX3CR1 regulated HCC cell metastasis via PI3K/AKT signaling and this effect might be a new target for clinical diagnosis and treatment.